Body iron stores and risk of type 2 diabetes: results from the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam study.

AIMS/HYPOTHESIS: The aim of this study was to prospectively examine the association between body iron stores and risk of type 2 diabetes. METHODS: We designed a case-cohort study among 27,548 individuals within the population-based European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam study. During 7 years of follow-up, 849 incident cases of type 2 diabetes were identified. Of these, 607 remained for analyses after exclusion of participants with missing data or abnormal glucose levels at baseline. A sub-cohort of 2,500 individuals was randomly selected from the full cohort, comprising 1,969 individuals after applying the same exclusion criteria. RESULTS: After adjustment for age, sex, BMI, waist circumference, sports activity, bicycling, education, occupational activity, smoking habit, alcohol consumption and circulating levels of γ-glutamyltransferase, alanine aminotransferase, fetuin-A, high-sensitivity C-reactive protein, adiponectin, HDL-cholesterol and triacylglycerol, higher serum ferritin concentrations were associated with a higher risk of type 2 diabetes (RR in the highest vs lowest quintile, 1.73; 95% CI 1.15, 2.61; p(trend) = 0.002). No significant association was observed for soluble transferrin receptor (RR 1.33; 95% CI 0.85, 2.09; p(trend) = 0.50). The soluble transferrin receptor-to-ferritin ratio was significantly inversely related to risk (RR 0.61; 95% CI 0.41, 0.91; p(trend) = 0.02). CONCLUSIONS/INTERPRETATION: High ferritin levels are associated with higher risk of type 2 diabetes independently of established diabetes risk factors and a range of diabetes biomarkers whereas soluble transferrin receptor concentrations are not related to risk. These results support the hypothesis that higher iron stores below the level of haemochromatosis are associated with risk of type 2 diabetes.

Reliability of fasting plasma alkylresorcinol metabolites concentrations measured 4 months apart.

Alkylresorcinols (AR) have been suggested as specific dietary biomarkers of whole-grain wheat and rye intake. AR are metabolised to 3,5-dihydroxybenzoic acid (DHBA) and 3-(3,5-dihydroxyphenyl)-1-propanoic acid (DHPPA), which have longer apparent half-lives and were recently proposed to better reflect long-term whole-grain consumption than the intact AR. The objective of this study was to analyse the reliability--expressed by the intraclass correlation coefficient (ICC)--of AR metabolite concentrations among 100 participants from the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam study who provided two fasting plasma samples 4 months apart. DHBA and DHPPA concentrations were not significantly different between the first and second measurement over the 4-month period (P>0.05). The ICC was 0.32 (95% confidence interval (CI)=0.13-0.49) for DHBA and 0.37 (95%CI=0.19-0.53) for DHPPA. These results suggest that AR metabolites cannot be considered to be better biomarkers of whole-grain wheat and rye intake than the intact AR in fasting plasma (ICC=0.42).

Association of changes in body mass index during earlier adulthood and later adulthood with circulating obesity biomarker concentrations in middle-aged men and women.

AIMS/HYPOTHESIS: The objective of our study was to investigate whether changes in BMI during earlier adulthood are more strongly associated with levels of circulating obesity biomarkers in middle age than are BMI changes during later adulthood. METHODS: The study included 1,612 participants from the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam Study. The associations of BMI changes based on recalled BMI for the age ranges 25-40 years (earlier adulthood) and 40-55 years (later adulthood) with later biomarker levels were compared using a linear model, adjusted for BMI at age 25 years and conventional risk factors. RESULTS: BMI changes during both time periods as well as BMI at age 25 years were significantly associated with circulating levels of adiponectin, γ-glutamyltransferase (GGT), alanine aminotransferase (ALT), high-sensitivity C-reactive protein (hs-CRP) and HDL-cholesterol (HDL-C) in both sexes, and of HbA(1c) in women. However, BMI gain for the age range 25-40 years was significantly more strongly associated with unfavourable levels of adiponectin, hs-CRP, HDL-C and HbA(1c) in men and women, and of GGT and ALT in men (p difference <0.05) than BMI gain for the age range 40-55 years. The percentage change in biomarker levels per unit gain in BMI for the age range 25-40 years ranged from 0.81% (HbA(1c)) to 9.80% (hs-CRP) in men, and from 0.75% (HbA(1c)) to 14.7% (hs-CRP) in women, whereas for the age range 40-55 years, values ranged from -0.15% to 4.82% in men and from 0.25% to 7.06% in women. CONCLUSIONS/INTERPRETATION: The results support the hypothesis that an increase in BMI in earlier adulthood is more strongly associated with unfavourable circulating levels of obesity biomarkers later in life than is an increase in BMI in later adulthood.

Reliability of fasting plasma alkylresorcinol concentrations measured 4 months apart.

BACKGROUND/OBJECTIVES: Alkylresorcinols (ARs) have been suggested as specific dietary biomarkers of whole-grain intake. Evaluation of long-term reliability in repeatedly collected samples in population-based studies is needed to assess whether plasma AR reflect long-term exposure and may be used to study exposure-disease relationships in large-scale epidemiologic studies. The objective of this study was to analyze the reliability (reproducibility) of AR concentrations in fasting plasma measured 4 months apart. SUBJECTS/METHODS: AR concentrations (C17:0, C19:0, C21:0, C23:0 and C25:0 and total ARs) were measured in fasting plasma samples from 100 participants from the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam Study with an interval of 4 months between blood sampling. RESULTS: Fasting plasma AR concentrations were not significantly different between the first and second measurement over the 4-month period. Geometric means of total AR concentrations were 48.8 (95% confidence interval (CI)=41.5-57.3) nmol/l at the first and 48.7 (95% CI=41.4-57.4) nmol/l at the second measurement (P=0.99). The intraclass correlation coefficients for total AR concentrations were 0.42 (95% CI=0.25-0.57) for all, 0.55 (95% CI=0.32-0.72) for women, and 0.17 (95% CI=-0.11-0.42) for men. Comparable results were obtained for the individual homologues. CONCLUSIONS: Overall, we observed moderate reliability in concentration of total AR and individual homologues over time, although reliability was weaker in men than in women. These findings should be taken into account when using AR as blood biomarkers for whole-grain intake in large-scale epidemiologic studies.

Malignancies in cases with screening-identified evidence of coeliac disease: a long-term population-based cohort study.

BACKGROUND AND AIMS: The association between diagnosed coeliac disease and malignancy has been established. The present study was conducted to determine whether previously unrecognised and thus untreated adults with screening-identified evidence of coeliac disease carry an increased risk of malignancies. METHODS: A Finnish population-based adult-representative cohort of 8000 individuals was drawn in 1978-1980. Stored sera of the participants with no history of coeliac disease or any malignancy were tested for immunoglobulin A (IgA) class tissue transglutaminase antibodies (Eu-tTG) in 2001. Positive sera were further analysed by another tissue transglutaminase antibody test (Celikey tTG) and for endomysial antibodies (EMAs). Malignant diseases were extracted from the nationwide database and antibody-positive cases were compared with negative cases during a follow-up of nearly 20 years. RESULTS: Altogether 565 of all the 6849 analysed serum samples drawn in 1978-80 were Eu-tTG positive. In further analyses, 202 (2.9%) of the participants were Celikey tTG positive and 73 (1.1%) were EMA positive. The overall risk of malignancy was not increased among antibody-positive cases in the follow-up of two decades; the age- and sex-adjusted relative risk was 0.91 (95% CI 0.60 to 1.37) for those who were Celikey tTG positive and 0.67 (95% CI 0.28 to 1.61) for those who were EMA positive. CONCLUSIONS: The prognosis of adults with unrecognised coeliac disease with positive coeliac disease antibody status is good as regards the overall risk of malignancies. Thus, current diagnostic practice is sufficient and there is no need for earlier diagnosis of coeliac disease by mass screening on the basis of the findings of this study.

Food consumption and the incidence of type II diabetes mellitus.

OBJECTIVE: The consumption of different foods was studied for their ability to predict type II diabetes mellitus. DESIGN: The study design was a cohort study, based on the Finnish Mobile Clinic Health Examination Survey. SETTING: A total of 30 communities from different parts of Finland. SUBJECTS: A total of 4304 men and women, 40-69 y of age and free of diabetes at baseline in 1967-1972 and followed up for incidence of diabetes medication during 23 y (383 incident cases). RESULTS: Higher intakes of green vegetables, fruit and berries, oil and margarine, and poultry were found to predict a reduced risk of type II diabetes. The relative risks of developing type II diabetes between the extreme quartiles of the intakes were 0.69 (95% confidence interval (CI) = 0.50-0.93; P for trend (P) = 0.02) for green vegetables, 0.69 (CI = 0.51-0.92; P = 0.03) for fruit and berries, 0.71 (CI = 0.52-0.98; P = 0.01) for margarine and oil, and 0.71 (CI = 0.54-0.94; P = 0.01) for poultry. CONCLUSION: The results suggest that prevention of type II diabetes might be aided by consumption of certain foods that are rich in nutrients with hypothesized health benefits.

Heart rate adjustment of magnetic field map rotation in detection of myocardial ischemia in exercise magnetocardiography.

AIMS: We studied the capability of heart rate (HR) adjusted change in multichannel magnetocardiogram (MCG) to detect exercise-induced ischemia. METHODS AND RESULTS: The MCG and 12-lead ECG were recorded simultaneously during supine exercise testing in 17 healthy controls and 24 patients with single vessel coronary artery disease (CAD). In the MCG analysis, we plotted the orientation of the magnetic field map (MFM) against the HR in each cardiac cycle during recovery. A regression line was fitted to the data and the line slope (degrees/bpm) was determined. In the ECG, the ST-segment depression vs HR (ST/HR) slope was evaluated. The HR adjusted MFM rotation was more extensive in the pooled CAD group, and in all subgroups with different stenosed vessel, than in the control group at the ST-segment (1.5 +/- 2.1 degrees/bpm vs 0.29 +/- 0.25 degrees/bpm, p < 0.0005) and at the T-wave apex (0.95 +/- 0.81 degrees/bpm vs 0.24 +/- 0.25 degrees/bpm, p < 0.0005). Areas under the receiver operating characteristic curves of the HR adjusted MFM rotation at the ST-segment (88.5%) and the T-wave (86.0%) were higher than the ones without HR adjustment (75.5% and 68.1%, respectively), and higher than the area of ST/HR slope in the ECG (80.2%). CONCLUSION: HR adjusted MFM rotation detects transient ischemia independent of the stenosed vessel. HR adjustment improves the performance of the MCG in ischemia detection by the analysis of the ST-segment and the T-wave. The MCG was superior to the 12-lead ECG.

Postmyocardial infarction patients susceptible to ventricular tachycardia show increased T wave dispersion independent of delayed ventricular conduction.

INTRODUCTION: Experimentally, both delayed ventricular conduction and nonhomogeneous ventricular repolarization contribute to reentrant arrhythmias. We tested the hypothesis that increased T wave dispersion is independent of delayed ventricular conduction associated with arrhythmia vulnerability in postmyocardial infarction (post-MI) patients. METHODS AND RESULTS: We studied 32 post-MI patients with clinical or inducible monomorphic ventricular tachycardia (VT group), 28 post-MI patients without arrhythmias (MI group), and 13 healthy controls, using magnetocardiographic (MCG) mapping with signal averaging. Twelve-lead ECG was the reference. Filtered QRS duration (fQRS) and T wave peak to T wave end interval (TPE) were used as measures of ventricular conduction and nonhomogeneity in ventricular repolarization, respectively. In MCG, the VT group showed the longest fQRS (135+/-34 msec vs 114+/-22 msec in the MI group; P = 0.012). Mean TPE and maximum TPE in VT versus MI groups were 78+/-9 msec versus 70+/-6 msec (P < 0.001) and 117+/-23 msec versus 104+/-19 msec (P = 0.020), respectively. Maximum TPE did not correlate with fQRS in the VT group (r = 0.063; P = NS) but did correlate in the MI group (r = 0.396; P = 0.037). For identification of post-MI patients prone to VT, selection of cutoff values for fQRS >140 msec and mean TPE >81 msec gave sensitivity and specificity of 41% and 89%, and 31% and 96%, respectively. Their combination increased sensitivity to 63% while maintaining 89% specificity. CONCLUSION: Post-MI patients susceptible to VT show increased T wave dispersion independent of delayed ventricular conduction.

Recording locations in multichannel magnetocardiography and body surface potential mapping sensitive for regional exercise-induced myocardial ischemia.

INTRODUCTION: This study aimed to identify the optimal locations in multichannel magnetocardiography (MCG) and body surface potential mapping (BSPM) to detect exercise-induced myocardial ischemia. METHODS: We studied 17 healthy controls and 24 coronary artery disease (CAD) patients with stenosis in one of the main coronary artery branches: left anterior descending (LAD) in 11 patients, right (RCA) in 7 patients, and left circumflex (LCX) in 6 patients. MCG and BSPM signals were recorded during a supine bicycle stress test. The capability of a recording location to separate the groups was quantified by subtracting the mean signal amplitude of the normal group from that of the patient group during the ST segment and at the T-wave apex, and dividing the resulting amplitude difference by the corresponding standard deviation within all subjects. RESULTS: In MCG the optimal location for ST depression was at the right inferior grid for the RCA, at the mid-inferior grid for the LCX, and in the middle of these locations for the LAD subgroup (mean ST amplitudes: CAD -80 +/- 360fT, controls 610 +/- 660fT; p < 0.001). In BSPM it was on the left upper anterior thorax for the LAD, left lower anterior thorax for the RCA, and on the lower back for the LCX subgroup (mean ST amplitudes: CAD -39 +/- 61 microV and controls 38 +/- 38 microV; p < 0.001). In MCG the optimal site for T-wave amplitude decrease was the same as the one for the ST depression. In BSPM it was on the middle front for the LAD, on the back for the LCX and on the left abdominal area for the RCA group. In accordance with electromagnetic theory, the largest ST segment and T-wave amplitude changes took place in MCG in locations orthogonal to those in BSPM. CONCLUSION: This study identified magnetocardiographic and BSPM recording locations which are sensitive for detecting transient myocardial ischemia by evaluation of the ST segment as well as the T-wave. These locations strongly depend on ischemic regions and are outside the conventional 12-lead ECG recording sites.

Magnetocardiographic intra-QRS fragmentation analysis in the identification of patients with sustained ventricular tachycardia after myocardial infarction.

The aim of this study was to investigate if magnetocardiographic (MCG) analysis of cardiac micropotentials within the QRS complex can identity patients prone to ventricular arrhythmias, and to compare it to MCG time-domain, late-field analysis. The study population consisted of 136 patients with remote MI, 53 with and 83 without a history of VT. After averaging and high pass filtering of multichannel MCG signals, time-domain parameters describing the end-QRS activity and fragmentation index M and score S describing the whole QRS complex were computed. Fragmentation and time-domain parameters differed between the VT and control groups: fragmentation index M was 12 +/- 3 versus 9 +/- 2 (P <0.001), fragmentation score S was 83 +/- 42 versus 56 +/- 21 (P < 0.001), and filtered QRS duration was 144 +/- 32 versus 114 +/- 19 ms (P < 0.001) in VT and control groups, respectively. A combination of fragmentation parameters yielded 87% sensitivity and 61% specificity in VT identification. Corresponding figures for a time-domain parameter combination were 81% and 72%. Sensitivity of time-domain analysis was 88% and specificity was 75% in a subgroup with anterior MI. In multivariate analysis, fragmentation and time-domain analyses discriminated VT patients from controls independently of the extent of coronary artery disease or left ventricular dysfunction. MCG in postinfarction patients reveals pathology associated with propensity to ventricular arrhythmias inside and not only at the end of the QRS complex. MCG seems most accurate in the anterior infarct location.

Beat-to-beat analysis method for magnetocardiographic recordings during interventions.

Multichannel magnetocardiography (MCG) during exercise testing has been shown to detect myocardial ischaemia in patients with coronary artery disease. Previous studies on exercise MCG have focused on one or few time intervals during the recovery period and only a fragment of the data available has been utilized. We present a method for beat-to-beat analysis and parametrization of the MCG signal. The method can be used for studying and quantifying the changes induced in the MCG by interventions. We test the method with data recorded in bicycle exercise testing in healthy volunteers and patients with coronary artery disease. Information in all cardiac cycles recorded during the recovery period of exercise MCG testing is, for the first time, utilized in the signal analysis. Exercise-induced myocardial ischaemia was detected by heart rate adjustment of change in magnetic field map orientation. In addition to the ST segment, the T wave in the MCG was also found to provide information related to myocardial ischaemia. The method of analysis efficiently utilizes the spatial and temporal properties of multichannel MCG mapping, providing a new tool for detecting and quantifying fast phenomena during interventional MCG studies. The method can also be applied to an on-line analysis of MCG data.

Magnetocardiographic QT dispersion during cardiovascular autonomic function tests.

QT dispersion is considered to reflect nonhomogeneity of ventricular repolarization. The autonomic nervous system modulates QT interval duration, but the effect may not be spatially homogenous. Magnetocardiography (MCG) registers the weak magnetic fields generated by myocardial electric currents with high localizing accuracy. We studied the effects of rapid cardiovascular autonomic nervous adjustment on QT dispersion in MCG. Ten healthy male volunteers were monitored during deep breathing, the Valsalva maneuver, sustained handgrip, hyperventilation, the cold pressor test and mental stress. 67 MCG channels and 12 ECG leads were recorded simultaneously. A computer algorithm was used for QT interval measurements. QT dispersion was defined as maximum - minimum or standard deviation of the QTpeak and QTend intervals. In MCG the QT(end) dispersion increased during deep inspiration compared with deep expiration (96+/-19 ms v. 73+/-27 ms, p = 0.05). Magnetic QT dispersion tended to increase during the bradycardia phase of the Valsalva maneuver, but the change was obvious only for QT(end) (55+/-26 ms v. 76+/-29 ms, p<0.05). Other tests had no significant effect on QT dispersion, not even the cold pressor test, although it causes strong sympathetic activation. Magnetic and electric QT(peak) and QT(end) intervals correlated closely (r = 0.93 and 0.91), whereas the QT dispersion measures showed no correlation. In conclusion, magnetic QT dispersion is not modified by rapid changes in autonomic tone, but maneuvers involving deep respiratory efforts and changes in ventricular loading affect QT dispersion measurements.

Effects of cardiovascular autonomic function tests on QT dispersion in the 12-lead electrocardiogram of healthy patients.

Changes in autonomic tone modulate QT interval duration. How cardiovascular autonomic reflexes affect QT dispersion, a suggested marker of arrhythmia risk, is not well established. We studied 10 healthy young adult volunteer men during quiet and deep breathing, the Valsalva maneuver, sustained handgrip, hyperventilation, the cold pressor test, and mental stress. An automated method was used for measurement of QT-peak and QT-end intervals, and QT dispersion was defined as maximum-minimum of the measured intervals. QT-peak dispersion was greater on deep expiration than deep inspiration (49 +/- 20 ms vs 37 +/- 14 ms, P < .05). QT-end dispersion decreased in the tachycardia phase of the Valsalva maneuver (45 +/- 23 ms vs 35 +/- 21 ms, P < .05), but QT dispersion did not change during the other interventions. Rapid cardiovascular autonomic reflex adjustment does not change QT dispersion in healthy young adult men. However, large intrathoracic volume and intrathoracic pressure changes during forced respiratory movements might confound QT dispersion measurements.

Late fields of the magnetocardiographic QRS complex as indicators of propensity to sustained ventricular tachycardia after myocardial infarction.

INTRODUCTION: Magnetocardiographic (MCG) mapping is a new method to record cardiac signals. This study examined the association of MCG late fields with the propensity to sustained ventricular tachycardia (VT) after myocardial infarction (MI). METHODS AND RESULTS: One hundred patients with remote MI were studied, 38 with and 62 without history of VT. High-resolution MCG and signal-averaged ECG (SAECG) as a comparative method were recorded. Time-domain parameters describing the abnormal low-amplitude end QRS activity, MCG late fields, and SAECG late potentials were analyzed. Late field parameters differed significantly between the patient groups: filtered QRS duration was 137 +/- 26 msec in the VT group and 110 +/- 18 msec in the control group (P < 0.001), and root mean square amplitude of the last 40 msec was 260 +/- 170 and 510 +/- 360 fT (P < 0.001), respectively. The optimal MCG parameter combination yielded a sensitivity of 92% and a specificity of 61% in classification to the VT group, whereas those for SAECG were 63% and 66%. In a subgroup of 63 patients with marked left ventricular dysfunction and comparable stage of coronary heart disease, only MCG (sensitivity 73%, specificity 67%) but not SAECG could assign a patient to the VT group. CONCLUSION: Late fields of the MCG QRS complex indicate propensity to life-threatening arrhythmias in post-MI patients. This discriminative ability persists in the presence of severe left ventricular dysfunction where ECG late potentials lose their informative value. MCG late field analysis is a potential new method for noninvasive risk assessment in post-MI patients.

Identification of post-myocardial infarction patients with ventricular tachycardia by time-domain intra-QRS analysis of signal-averaged electrocardiogram and magnetocardiogram.

A new time-domain analysis method, which quantifies ECG/MCG intra-QRS fragmentation, is applied to parts of the QRS complex to identify post-myocardial infarction patients with ventricular tachycardia. Three leads of signal-averaged electrocardiograms and nine leads of magnetocardiograms were band-pass filtered (74 Hz to 180 Hz). The filtered signals showed fragmentation in the QRS region, which was quantified by the number of peaks M and a score S, that is the product of M and the sum of the peak amplitudes. Both parameters were determined for the first 80 ms of the QRS complex and the total QRS complex in each channel. For classification, the mean-values of the parameters M and S of the three electrical leads and the nine magnetic leads were calculated. Late potential and late field analyses were performed for the same signals. 31 myocardial infarction patients were included, 20 of them with a history of documented ventricular tachycardia (VT). Identification of VT patients using the SAECG led to better results (sensitivity 95%, specificity 91%) considering the entire QRS complex than with the standard late potential analysis suggested by Simson (sensitivity 90%, specificity 73%). For the SAMCG and the entire QRS complex results using the parameters S and M are also better (sensitivity 95%, specificity 100%) than for the late field analysis (sensitivity 90% and specificity 100%). For the first 80 ms, the performance of the parameters M and S is only slightly decreased.

Non-invasive arrhythmia risk evaluation in clinical environment.

We have applied various methods to extract parameters from high-resolution magnetocardiographic (MCG) and electrocardiographic (ECG) recordings for characterizing the risk of life-threatening arrhythmias. The methods include detection of late fields and late potentials at the end of the QRS, abnormalities in spectral variability and signal fragmentation during the QRS, and variability in the heart rate. In addition, we have developed methods to convert MCG signals measured with any sensor configurations to a common presentation form. The signal processing methods have been implemented on a user-friendly interface which allows fast and easy use in a clinical environment.

Magnetocardiographic QT interval dispersion in postmyocardial infarction patients with sustained ventricular tachycardia: validation of automated QT measurements.

QT dispersion is a measure of heterogeneity in ventricular repolarization. Increased ECG QT dispersion is associated with life-threatening ventricular arrhythmias. We studied if magnetocardiographic (MCG) measures of QT dispersion can separate postmyocardial infarction patients with and without susceptibility to sustained VT. Manual dispersion measurements were compared to a newly adapted automatic QT interval analysis method. Ten patients with a history of sustained VT (VT group) and eight patients without ventricular arrhythmias (Controls) were studied after a remote myocardial infarction. Single-channel MCGs were recorded from 42 locations over the frontal chest area and the signals were averaged. QT dispersion was defined as maximum-minimum or standard deviation of measured QT intervals. VT group showed significantly more QT and JT dispersion than Controls. QTapex dispersions were 127 +/- 26 versus 83 +/- 21 ms (P = 0.004) and QTend dispersions 130 +/- 37 versus 82 +/- 37 ms (P = 0.013), respectively. Automatic method gave comparable values. Their relative differences were 9% for QTapex and 27% for QTend dispersion on average. In conclusion, increased MCG QT interval dispersion seems to be associated with a susceptibility to VT in postmyocardial infarction patients. MCG mapping with automated QT interval analysis may provide a user independent method to detect nonhomogeneity in ventricular repolarization.

Noninvasive risk modeling after myocardial infarction.

The aim of this study was to extract and combine non-invasive risk parameters from the signal-averaged electrocardiogram (SAECG) and heart rate variability (HRV) based on 24-hour ambulatory electrocardiography to optimize the prognostic value for arrhythmic events after acute myocardial infarction. A prospective series of 553 men < 66 years of age enrolled in the Post-Infarction Late Potential study were analyzed. Within 2 to 4 weeks after acute myocardial infarction, all patients underwent SAECG and 24-hour ambulatory electrocardiography before hospital discharge. During 6 months of followup, 25 patients (4.5%) experienced arrhythmic events (sustained ventricular tachycardia, n = 11; ventricular fibrillation, n = 7; sudden cardiac death, n = 7). The predictive power of SAECG and HRV parameters was assessed using a Cox proportional-hazards model. In HRV analysis, the most significant differences between patients with and without arrhythmic events were observed for the beat-to-beat parameter root-meansquare of successive RR differences [RMSSD]): 25.7 +/- 16.9 ms in patients with arrhythmic events versus 34.1 +/- 18.6 ms in patients free of arrhythmic events (p = 0.004). Time domain analysis of the SAECG showed the QRS duration to be most significantly different in both patient groups: 106.4 +/- 18.7 ms (arrhythmic events) versus 95.3 +/- 18.7 ms (no arrhythmic events) (p = 0.001). Based on the Cox regression model, RMSSD and QRS duration were demonstrated to be independent significant risk factors (regression coefficient for QRS duration: cq = 0.014 +/- 0.006 ms(-1), p = 0.014; for RMSSD: cr = -0.041 +/- 0.016 ms(-1), p = 0.009). Based on the regression coefficients, an analytic risk model was developed describing the arrhythmic risk as a function of QRS duration, RMSSD, and time after infarction. We conclude that the combination of beat-to-beat changes of heart rate measured by RMSSD and QRS duration from the SAECG enhances noninvasive risk stratification after myocardial infarction.

Predictive value of wavelet correlation functions of signal-averaged electrocardiogram in patients after anterior versus inferior myocardial infarction.

OBJECTIVES: This study sought to evaluate the prognostic value of wavelet correlation functions of the signal-averaged electrocardiogram (ECG) for arrhythmic events in patients after myocardial infarction. BACKGROUND: Wavelet transform of the signal-averaged ECG has been shown to be a nonstationary analysis technique describing the time evolution of frequency spectra throughout the QRS complex. To quantify the wavelet transform, we introduced the new concept of the wavelet correlation function. METHODS: The relation among wavelet correlation functions, ventricular late potentials and the site of infarction was investigated in 769 men < 66 years old who survived the acute phase of myocardial infarction (351 [46%] anterior, 418 [54%] inferior infarctions). Signal-averaged ECG recordings were obtained 2 to 3 weeks after infarction. During 6 months of follow-up, 33 patients (4.3%) experienced a malignant arrhythmic event. Wavelet correlation functions of the signal-averaged ECG were evaluated in a time-frequency plane ranging from 25 ms before QRS onset to 25 ms after QRS offset in the frequency range between 40 and 100 Hz. RESULTS: Patients with an anterior infarction had lower mean wavelet correlation coefficients (p < 0.001) and a lower incidence of ventricular late potentials than patients with an inferior infarction (32.3% vs. 42.7%, p = 0.003). The combination of wavelet correlation functions and late potentials increased the total predictive accuracy from 52% to 72% for inferior and from 64% to 76% for anterior infarctions. CONCLUSIONS: Spectral changes in the signal-averaged QRS complex are more prominent in anterior than inferior infarctions. Combination of late potential analysis and wavelet correlation functions increases the prognostic value for serious arrhythmic events after myocardial infarction.

Transformation of multichannel magnetocardiographic signals to standard grid form.

Multichannel magnetocardiographic (MCG) recordings with fixed sensor arrays are not directly comparable with single-channel measurements carried out at standard grid locations. In addition, comparison of data obtained with different types of magnetometers is difficult. We present a method for transforming multichannel measurements to the standard-grid format. The minimum-norm estimate (MNE) of the source current distribution in the body is calculated, and the desired field components in standard grid points are then computed from the MNE. We measured three subjects with both a 24-channel and a single-channel instrument. The signals extrapolated from the multichannel measurements corresponded quite well to the single-channel data registered at the standard grid locations, especially in those grid points that were covered by the 24-channel device. The signal-amplitude-weighted correlations between the extrapolated and directly measured signals were 0.73-0.87. In simulations with ideal measurement geometry but with a realistic amount of random noise in the signals, we obtained a 0.99 correlation. It was also found that the method is relatively tolerant to errors in the location and orientation of the multichannel magnetometer. For example, a simulated 20-mm displacement in the location of the sensor array caused only a 3% decrease in the correlation, and when it was rotated and tilted by 10 degrees C, the correlation decreased by 5%. The basic advantage of our extrapolation method is its physiologic nature: the method is based on the mathematical modeling of the source current distribution, rather than on direct constraints applied to the magnetic field.